How Photosensitization Can Stop Viruses from Infecting Cells

Get familiar with the Light Zaps Viruses and Photosensitization and how it can stop the viruses from spreading and infecting the cells.

By Jaime Abella Sison, DVM

A University of California, Los Angeles (UCLA)-led team of researchers has found evidence that photosensitizing a virus’ membrane covering can inhibit its ability to enter cells and potentially lead to the development of stronger, cheaper medications to fight a host of tough viruses, according to Science Daily last March 4, 2014.

The UCLA AIDS Institute study, published in the February 2014 issue of the Journal of Virology, is part of ongoing research on a compound called LLJ001, a “broad-spectrum” antiviral that can attack a wide range of microbes.

The current paper advances the science by showing that the process of photosensitization—heightening a biological organism’s sensitivity to certain damaging processes induced by light—applies to more than just LJ001. This could pave the way for a cost-effective way to make blood products safer, which is particularly important in resource-poor countries where deadly viruses are rampant.

Combating two categories of viruses with photosensitizers There are two categories of viruses: lipid-enveloped and non-enveloped. Enveloped viruses, including many that are of great public health concern, have a membrane that serves as a mechanism through which the microbe inserts its genome into a host cell, infecting it.

Photosensitizers, which have the ability to damage a virus’ genetic material, can in many cases prevent infection, according to first author Frederic Vigant, who conducted the study as a postdoctoral researcher in microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.

PHOTO-OXIDATION OF LIPIDS – “The ability of photosensitizers to inactivate many different viruses has been known for decades,” Vigant said, pointing out their well-known ability to cross-link the DNA and RNA of lipid-enveloped viruses, causing irreversible damage. “It must have seemed so obvious this was how photosensitizers work that no one ever looked in detail at the oxidation of the lipids. Oxidation of lipids by light—termed photo-oxidation— is also very well-known.”

For the current study, an international research team led by Dr. Benhur Lee—adjunct professor of microbiology, immunology and molecular genetics at the Geffen School— nailed down how photo-oxidation of the viral lipid envelopecan be a general method for compromising the ability of such viruses to enter cells.

In an earlier proof-of-principle study published in 2010, the researchers described an antiviral small molecule – a rhodanine derivative they dubbed LK001 – that is effective against numerous viruses, including HIV-1, influenza
A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, and flaviviruses. These viruses cause some of the world’s deadliest diseases, such as AIDS, Nipah virus encephalitis, Ebola hemorrhagic fever, and Rift Valley fever. This LJ001 compound could also be effective against new, yet-to-be discovered enveloped viruses, the researchers said.In a subsequent paper published in April 2013 in PLOS
Pathogens, the team found that the LJ001 broad-spectrum antiviral, and its more potent second-generation derivatives, could affect not just some but any lipid-enveloped virus via photosensitization of the envelope. It was first time this process was identified and used as an antiviral strategy, Lee
said.

NEW PARADIGM FOR ANTIVIRALS – The new Journal of Virology paper, Lee said, shows that this new paradigm for antivirals applies to more than just
LJ001. The team examined another broad-spectrum antiviral compound called dUY11, which has been thought to act as a “wedge” by inserting itself into viral membranes and compacting the lipids, impairing fusion and entry into cells.The new research demonstrates that the process is unlikely to happen on its own because it is inactive in the dark. It turned
out to behave as a photosensitizer in all the experiments they performed.

As with LJ001 and its derivatives, dUY11 enters the viral membranes, is activated by light, and then changes the lipid composition of the viral coating, resulting in the inability of the virus to fuse with and enter cells.

“In other words, instead of the compound itself acting as a physical constraint on the membrane, we show that it actually works through photochemical reactions that end up changing the biophysical properties of the virus membrane that make it unable to mediate fusion,” Vigant said.

A DIFFERENT APPROACH TO PEDV – With the continued spread of PEDv (Porcine Epidemic Diarrhea virus) in the United States, Canada, and the
Philippines, biosecurity measures have been reaffirmed as the main precautions producers can take against the virus. But what else should producers take a look at?

In a recent release, Dr. Karl Dawson, Chief Scientific Officer at Alltech, cautioned producers to work closely with veterinarians to implement stringent biosecurity measures and a nutritional management program that strengthens the pigs’ immunity and disease defenses.

Producers should also identify key interactions where there is a risk of exposure and ensure safety standards are in place. Proper cleaning with disinfectants, heating and drying helps to destroy the virus. Some areas that have been determined to be high risk are dead haul/renderer sites,
pests in the barns, personnel who also work at other pig farms, recently removed culled pigs, and newly-weaned pigs transported to the nursery or finishing site.

“While it is unrealistic to believe that a simple nutritional change will result in the elimination of the virus from a herd of pigs,” Dawson said, “Alltech’s distinct set of technologies can help in maintaining healthy pig populations, which is the first step in dealing with a herd crisis.” These technologies include solutions that have been shown to help maintain gastrointestinal health and wellbeing.

Using these nutritional strategies helps to ensure pigs are performing at their peak, optimizing their immunity and giving them the best change to protect themselves.